Addressing Tamoxifen-Associated Weight Gain: Lifestyle and Pharmacotherapy Options

Tamoxifen, a selective estrogen receptor modulator (SERM), is commonly prescribed in hormone receptor-positive breast cancer. While effective in reducing recurrence and mortality, tamoxifen is associated with weight gain in a significant proportion of patients. This weight gain complicates survivorship care, particularly given obesity's association with recurrence risk and all-cause mortality. Although lifestyle modification remains the standard of care for weight management, many breast cancer survivors struggle to achieve sufficient results with behavioral interventions alone. Current guidelines from oncology and obesity societies provide limited, nonspecific direction regarding pharmacologic weight management for tamoxifen-treated patients. Medication classes including GLP-1 receptor agonists, tirzepatide, phentermine-topiramate, bupropion-naltrexone, and orlistat are reviewed with attention to efficacy, safety, potential interactions, and tamoxifen-specific considerations. Practical monitoring strategies and prescribing considerations are provided to support oncology practitioners. This narrative review summarizes available evidence on tamoxifen-associated weight gain and outlines considerations for the use of anti-obesity medications in this population.